Compounds of general formula (I) that are antagonists of the Vanilloid subtype 1 receptor (VR1) were originally prepared via a synthetic route described in U.S. Ser. No. 10/864,068. The synthetic route in this invention relied upon treating a nitroanaline with sodium nitrite to form a nitroindazole intermediate. Recent developments have afforded a new highly efficient synthetic pathway, which generates fewer impurities and presents a more cost effective process for generating this valuable compound. The new route also incorporates the following innovative chemical methods: a new method for the preparation of 4-haloindazoles via condensation of the corresponding halogenated benzaldehydes or certain halogenated ketone substituted benzene rings with hydrazine; a method for the selective protection of haloindazoles at the N1 or N2 position and a method for the conversion of haloindazoles into indazoyl ureas.
Compounds of general formula (I) that are antagonists of the Vanilloid subtype 1 receptor (VR1) are useful in treating disorders associated with overactivity of the Vanilloid subtype 1 receptor a described in U.S. Ser. No. 10/864,068.